Study on the Effect of Cannabinoid Agonist on Gastrointestinal and Colonic Motor and Sensory Functions in Patients With Diarrhea-Predominant Irritable Bowel Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Colonic Compliance at Pressure at Half-Maximum Volume (Pr 1/2)
研究概览
简要总结
Irritable bowel syndrome (IBS) affects about 15% of the U.S. population. There are still no effective and safe medications approved for the treatment of abdominal pain associated with bowel symptoms in IBS. This study will investigate the effects of an approved medication, Dronabinol, on the movement of food through the stomach and colon in subjects with a history of diarrhea-predominant Irritable Bowel Syndrome (D-IBS).
详细描述
Irritable bowel syndrome (IBS) affects about 15% of the U.S. population. Despite increasing understanding of the pathophysiology of IBS, there is no effective medication approved for the treatment of abdominal pain associated with IBS. Cannabinoid receptors (CBR) are on cholinergic neurons in the brain stem, stomach and colon. A cannabinoid receptor 1 (CB1) antagonist, rimonabant, is effective in induction of weight loss; however, the mechanism of this benefit is unclear. Human studies from this lab show that a CBR agonist, dronabinol, inhibits gastric and colonic motility, which may alter appetite or satiation in obesity, and may have potential in the treatment of IBS. The overall focus of the study is on the mechanisms involved in the modulation of gastric and colonic motor and sensory functions by cannabinoid receptors (CBR) in health and in IBS. CB1 receptors are also involved in nociception and in mediating inflammation which are increasingly recognized as being potential pathophysiological mechanisms in IBS.
All participants underwent the following procedures:
- Documentation of eligibility, screening questionnaires and physical examination, including exclusion of rectal evacuation disorder by standard clinical evaluation within the past 12 months; this was important to ensure the diarrhea was not secondary to "retention with overflow".
- Bowel preparation with PEG and electrolyte-containing oral colonic lavage solution, followed by a 12 hour fast.
- Colonic testing of compliance, tone, motility and sensation measurement. Colonic compliance, fasting tone, sensory thresholds and sensory ratings in response to random-order phasic distensions were performed before treatment was administered. Then medication was ingested, and after 60 minutes, the same studies were performed that is compliance, fasting tone, sensory thresholds and sensory ratings in response to random-order phasic distensions. Participants also filled in responses to questionnaires (using 100 mm VAS scales) to describe their sense of tiredness, peace, worry and activity at the time of the measurements of sensation. Finally, participants ingested a standard chocolate 1000 kcal milkshake meal, and postprandial colonic tone and motility were measured for one hour.
- With appropriate consent, a venous blood sample was obtained from each participant for DNA extraction; this will be used in ongoing pharmacogenomics studies.
Note: This study is related to NCT01253408, part A of the same protocol. Part A explored the effect of dronabinol on gastric and colonic motor functions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-75 years
- •Positive for IBS symptoms by Rome III criteria
- •No prior abdominal surgery (except appendectomy or cholecystectomy
- •Score of 10 or less on either Anxiety or Depression on the Hospital Anxiety/Depression Inventory
排除标准
- •Patients with significant depression (score of greater than 10 on Hospital Depression Inventory
- •Patients with anxiety (score of greater than 10 on Hospital Anxiety Inventory. However, patients on stable doses of selective serotonin inhibitors (SSRIs) or low dose of tricyclic antidepressants will be eligible.
研究组 & 干预措施
Dronabinol 2.5 mg
One dose of dronabinol 2.5 mg was taken orally with water.
干预措施: Dronabinol (Drug)
Dronabinol 5 mg
One dose of dronabinol 5 mg was taken orally with water.
干预措施: Dronabinol (Drug)
Placebo
One dose of placebo was taken orally with water.
干预措施: Placebo (Drug)
结局指标
主要结局
Colonic Compliance at Pressure at Half-Maximum Volume (Pr 1/2)
时间窗: 1 hour after drug was ingested
Colonic compliance is a measure of the "stiffness" of the colon, that is, what pressure was needed to reach half the maximum volume of the colon. After the barostat catheter was inserted in the colon, the catheter was connected to a barostat machine. After an initial conditioning distension to 20 mm Hg, colonic compliance was measured by step-wise inflation with increments of 4 mm Hg up to 64 mm Hg. Colonic compliance was analyzed by a validated linear interpolation method. The pressure at half maximum volume serves as a summary of colonic compliance.
次要结局
- Postprandial Change in Colonic Tone(1 hour after ingestion of standard meal)
- Post-treatment Sensory Threshold for First Perception of Pain(1 hour after drug was ingested)
- Post-Treatment Overall Sensory Rating in Response to 16, 24, 32, and 40 mm Hg Distensions(1 hour after drug was ingested)
- Fasting Colonic Tone(After 12 hour fast, before drug administered)
- Postprandial Colonic Motility Index(1 hour after ingestion of standard meal)
- Post-treatment Sensory Threshold for First Sensation(1 hour after drug was ingested)
- Post-Treatment Sensory Threshold for First Perception of Gas(1 hour after drug was ingested)
研究者
Michael Camilleri
Professor of Medicine
Mayo Clinic